混合配列ボラン・フォスフォナートDNAの合成

Heather Brummel McCuen¹, Mary S Noé, Agnieszka B Sierzchala

¹Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA.

Journal of the American Chemical Society

|June 22, 2006

まとめ

新しい固体相合成法により,ボランフォスホン酸塩DNAの生成が可能になりました. この画期的な発見により,初めて,混合または独占的にボラン・フォスフォナート結合によるDNAの合成が可能になった.

科学分野:

有機化学オーガニック・ケミストリー
分子生物学は分子生物学である.
バイオケミストリーバイオケミストリー

背景:

ボランホスフォナートDNAは,潜在的な治療用途を持つ改変された核酸です.
改変DNAのための既存の合成方法には,特定の結合型を作成する際の制限があります.

研究の目的:

ボランフォスフォン酸塩DNAを合成するための新しい固体相フォスフォラミド酸塩ベースの方法を開発する.
混合または独占的にボランホスホネート核酸間結合を持つDNAの作成を可能にします.

主な方法:

固体相フォスフォラミジットベースのアプローチを使用しました.
標準の5'-ジメトキシトリチル阻害群を5'-シリルエーテルで置き換えました.
DNA塩基に対する新しい保護群を採用した:アデニン (N6-ジメトキシトリチル),サイトシン (N4-トリメトキシトリチル),グアニン (N2-[9-フッ素リルメトキシカルボニル]),チミン (N3-アニソイル).

主要な成果:

ボラン・フォスフォナートDNAを合成するための新しい方法を開発しました.
4つの2'-デオキシヌクレオシドの任意の組み合わせでオリゴデオキシヌクレオチドを生成する能力を実証した.
フォスファートとボランフォスフォナート双方の核酸間結合,特にボランフォスフォナート結合を含むDNAの合成を可能にします.

結論:

開発された方法は,ボランホスホン酸塩DNAを合成する以前の制限を克服しています.
この進歩は,研究および治療上の応用のために,ボランフォスホン酸塩結合による多様なDNA構造の作成を容易にする.

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